ORIGINAL ARTICLES
Predictive Values of Risk Factors in Neonatal Sepsis
MS HASANa, CB MAHMOODb
Summary:
Neonatal sepsis is one of the most important causes of
mortality and morbidity especially in developing countries.
Management of such cases is difficult, costly and need expert
centers in many cases. Therefore, identification of the risk
factors and their predictive values may help optimizing its
management. With the above idea this case-control study
was done to see the effects of maternal and neonatal risk
factors and to find their predictive values in the development
of neonatal sepsis. Fifty cases and fifty suitably matched
controls were enrolled in the study and different maternal,
natal and newborn factors were compared. Many risk factors
were found to have influence in the development of neonatal
sepsis. Among them the maternal intrapartum fever, foul
smelling liquor, young mother (< 20 yrs), poor income
Introduction:
Neonatal sepsis or septicemia is the term that have been
used to describe the systemic response to infection in
newborn infants during the first 28 days of life. There
are 2.8 million of neonatal deaths occur annually during
the first year of life in the world1. Mortality rates vary,
ranging from 12-30% in developing countries. 2,3 to 8.3
to 12.5 per 1000 live births in developed countries.4,5
While infant mortality has been declining all over the
world, changes in neonatal mortality rate has been much
slower in Bangladesh.1 The over all incidence of
neonatal sepsis varies between 1 and 4 cases per 1000
live births6 Infection accounts for 70 to 72.7% of
neonatal death.7,8
a. Dr. Mohammad Shameem Hasan, FCPS, Assistant Professor
(cc), Department of Child Health, Chittagong Medical College
Hospital
b. Prof. Chowdhury B. Mahmood, FCPS, Head of the Department,
Department of Child Health, Chittagong Medical College
Hospital
Address of Correspondence: Dr. Mohammad Shameem Hasan,
House no# 48, Road no # 04, O.R. Nizam Rd R/A, Chittagong.
Mail: dr.shamim_hasan@ymail.com
Received: 18 June 2008 Accepted: 20 September 2011
group, prolonged labor, unclean vaginal examination
(UVE) and primi mother were much associated with the
occurrence of sepsis. Also the neonatal factors, like
prematurity, resuscitation at birth and low APGAR score
carried the significant risk of developing sepsis. But when
relative influence of these risk factors were analyzed over
neonatal sepsis in detecting their predictive values, it was
found that irregular antenatal check up, prematurity,
resuscitation at birth, and maternal intrapartum fever had
influenced most in the development of neonatal sepsis in
chronological order.
Key words: Neonatal sepsis, maternal risk factors, neonatal
risk factors
(J Bangladesh Coll Phys Surg 2011; 29: 187-195)
The attack rate of neonatal sepsis varies geographically
depending on the prevalence of organism in the
community. The infection may be mild, moderate or
severe and acute, sub acute or chronic or it may be
asymptomatic. The absence of clinical signs at the time
of the initial physical examination does not preclude
infection.
Early manifestations of infection may be subtle and
nonspecific.9 Moreover accurate diagnosis of neonatal
sepsis is difficult because there is no definitive
diagnostic test; even blood cultures have an
unacceptably low sensitivity.
Cause, risk factors and consequences / sequel of sepsis
have not been adequately researched and clinical guide
lines for detection of sepsis by community health
workers have not been evaluated in Bangladesh. Even
we are not enriched with all required laboratory facilities
and sometimes we cannot bear the cost of all laboratory
expenses. Moreover nothing is known about
microorganism patterns and their antibiotic sensitivities
in community based neonatal sepsis of our country. So,
it is important for physicians at periphery to recognize
the early features of neonatal sepsis, because late
detection and referral, delayed antibiotic therapy and
Journal of Bangladesh College of Physicians and Surgeons Vol. 29, No. 4, October 2011

supportive care may lead to extensive unrecoverable
sepsis. Risk approach based identification can help all
to detect and treat neonatal sepsis and curb mortality.
Therefore detecting all maternal and neonatal risk
factors causing neonatal sepsis and relating them with
clinical and available laboratory findings neonates can
be discharged early from the hospital, stopping the
antibiotics, thereby reducing the cost of treatment and
anxiety of the family.
Materials and methods:
A total number of 50 cases were enrolled as case having
established sepsis and 50 cases were matched as control
having no established sepsis. This study was done in
Child Health Department of Chittagong Medical College
Hospital from 1st October 2002 to 31st March 2003.
Neonates who developed symptomatic sepsis within 28
days of birth irrespective of gestational age and birth
weight were included in this study. Those symptomatic
neonates who either had positive blood culture or had
total WBC count<5000/cmm, IT Ratio e0.2, CRP
e10mg/dl were regarded as case.5 Those symptomatic
neonates whose blood culture were found negative or
those having less than 3 negative screening test were
included as control. Cases with neonatal tetanus,
TORCH infection, and babies born to hepatitis B virus
infected mothers, congenital malformation, perinatal
asphyxia; RDS and babies who received antibiotics prior
to admission were excluded from this study.
On admission clinical histories were obtained including
perinatal history. Through physical examination of the
infants were done. All the relevant information was
recorded in a pre designed questionnaire and data was
compiled at the end of the study.
Results:
Risk factors influencing Neonatal Sepsis have been
plotted as Neonatal and Maternal Risk Factors in Table:
1 and Table: 2 respectively. Each risk factor was
individually analyzed against sepsis (using 2x2
contingency table I & II), to show their level of
significance in producing sepsis and were plotted in Table
III and Table IV respectively. Table V show frequency of
occurrence of individual risk factor. Table VI and also
the Chart: 1.1 and Chart: 1.2 shows the regression slope
and also the relative influence of risk factors over neonatal
sepsis highlighting predictive values.
Among 50 cases under study 39 were male and 11 were
female and among control 31 were male and 19 were
female. The frequency rate of sepsis is more in male
(55.7%) than female. The difference is, however,
statistically not significant (P >0.0810). Male showed
2.173 times greater risk of developing sepsis than female.

Table-I

Distribution of Neonatal Risk Factors

Character Casen (% ) Controln ( % )

Sex of the Baby Male 39 (55.7) 31(44.3)
Female 11 (36.7) 19(63.3)
Birth weight (grams) <2500 24(49) 25(51)
>2500 26(51) 25(49)
Gestational age in weeks <37 wks 16(72.7) 6(27.3)
>37wks 34(43.6) 44(56.4)
APGAR score<5 at 1min Yes 13(68.4) 6(31.6)
No 37(45.7) 44(54.3)
APGAR score<7 at 5min Yes 14(70) 6(30)
No 36(45) 44(55)
Use of AMBU bag/mouth to mouth breathing Yes 21(65.6) 11(34.4)
No 29(42.6) 39(57.4)

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Predictive Values of Risk Factors in Neonatal Sepsis MS Hasan & CB Mahmood

Table-II

Distributions of Maternal Risk Factors

Character Casen (% ) Controln ( % )

Age of Mother in years <20 yrs 30(66.7) 15(33.3)
>20 yrs 20(36.4) 35(63.6)
Parity Primipara 40(57.1) 30(42.9)
Multipara 10(33.3) 20(66.7)
Income group Poor 25(39.1) 39(60.9)
Average 25(69.4) 11(30.6)
Antenatal check up Irregular 36(45) 44(55)
Regular 14(70) 6(30)
Duration of labor in hours >24 hrs 37(60.7) 24(39.3)
< 24 hrs 13(33.3) 26(66.7)
Duration of Rupture of membrane in hours >24 hrs 30(58.8) 21(41.2)
< 24 hrs 20(40.8) 29(59.2)
No of Unclean Vaginal examination >3 times 30(61.2) 19(38.8)
< 3 times 20(39.2) 31(60.8)
Intrapartum fever Yes 22(78.6) 6(21.4)
No 28(38.9) 44(61.1)
Foul smelling liquor Yes 19(79.2) 5(20.8)
No 31(40.8) 45(59.2)

Table-III

Analysis of Neonatal Risk Factors influencing neonatal sepsis by level of significance

Character X2 df P
1 Sex of the Baby 3.048 1 0.081
2 Birth weight (grams) 0.040 1 0.841
3 Gestational age in weeks 5.828 1 0.016
4 APGAR score < 5 at 1 min 3.184 1 0.074
5 APGAR score <7 at 5 min 4.000 1 0.046
6 Use of AMBU /mouth to mouth breathing 4.596 1 0.032

Table-IV

Analysis of Maternal Risk Factors influencing neonatal sepsis by level of significance

Character X2 df P
1 Age of Mother in years 9.091 1 0.003
2 Parity 4.762 1 0.029
3 Income group 8.507 1 0.004
4 Antenatal check up 4.000 1 0.046
5 Duration of labor in hours 7.104 1 0.008
6 Duration of Rupture of membrane in hours 3.241 1 0.072
7 No of Unclean Vaginal examination 4.842 1 0.028
8 Intrapartum fever 12.698 1 0.000
9 Foul smelling liquor 10.747 1 0.001

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Journal of Bangladesh College of Physicians and Surgeons Vol. 29, No. 4, October 2011

Table-V

Individual risk factor for neonatal sepsis by frequency of occurrence

Risk factors Frequency of occurrence

1 Foul smelling liquor: (79.2%)
2 Intrapartum fever: (78.6%)
3 Gestational age <37wks: (72.7%)
4 APGAR<7at5min: (70%)
5 APGAR<5at1min: (68.4%)
6 Age of mother <20yrs: (66.7%)
7 Resuscitation at birth: (65.6%)
8 UVE>3: (61.2%)
9 Duration of labor >24 hrs: (60.7%)
10 PROM>24 hrs: (58.8%)
11 Primi Para (57.1%)
12 Male sex: (55.7%)
13 Birth weigh<2500gms 49%
14 Irregular ANC: 45%
15 Poor socioeconomic status 39.1%

Table-VI

Relative influence of risk factors over Neonatal sepsis (Multiple regressions)

Risk Factors B Significance

Sex (Male) 0.991 0.138
Birth weight (<2500 gms) -0.861 0.194
Gestational age (<37 wks) 1.772 0.027
APGAR score <5 at 1 min (yes) 0.125 0.906
APGAR score <7 at 5 min (yes) -0.217 0.843
Resuscitation at birth (yes) 1.578 0.071
Age of mother in years (<20 yrs) 0.995 0.137
Parity (Primi para) 0.498 0.488
Income group (poor) -0.651 0.275
Antenatal checkup (irregular) -1.885 0.017
Duration of labour (>24 hrs) 0.826 0.187
Duration of rupture membrane (>24 hrs) 2.651 0.969
Unclean vaginal examination (>3 times) 0.116 0.857
Intrapartum fever (yes) 1.638 0.089
Foul smelling liquor (yes) 0.120 0.904
(B= Beta, which stands for regression slope)

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Predictive Values of Risk Factors in Neonatal Sepsis
Effects of birth weight on neonatal sepsis showed that
24 neonate among cases and 25 among control had
LBW. But statistically LBW showed no significance (P
>0.841) in the development of neonatal sepsis.
Sixteen cases and six controls had gestational age < 37
weeks. 72.7 % of these babies developed sepsis, which
showed high statistical significance (P<0.016) in the
development of neonatal sepsis. They had 3.451 times
greater risk of developing sepsis than those having
gestational age of >37 weeks. Total 19 babies had an
APGAR score of <5 at 1 min of them 13(68.4%)
developed sepsis. Though the difference is not
statistically significant (P >0.074), they had 2.577 times
greater chance of developing sepsis than babies with
normal APGAR score. On the other hand 20 babies had
an APGAR score <7 at 5 min, of them 14(70%)
developed sepsis which is found to be statistically
significant (P<0.046) & the development chance of
sepsis was 2.852 times greater in this group.
Fig.-1: Relative influences of risk factors over Neonatal
sepsis (Multiple regressions) showing the regression
slope.
MS Hasan & CB Mahmood
Among 50 cases and 50 control 32 patients required
resuscitation at birth. 21 (65.6%) of them developed
sepsis and carried 2.567 times greater chance to develop
sepsis than those who did not require resuscitation
procedure. The finding was statistically significant
(P<0.032). Out of 50 cases and 50 controls 45 mothers
were found to be <20 years of age. Among them
30(66.7%) babies of these mothers had sepsis which is
3.5 times greater than babies born to mother having e
20 yrs of age. It was also found to be statistically
significant (P<0.003). Among 70 babies of total Primi
mothers 40(57.1%) had sepsis and carried 2.667 times
greater chance of sepsis than babies born to Multipara.
It was found to be significant (P<0.029).
Fig.-2: Relative influences of risk factors over Neonatal
sepsis (Multiple regressions) showing their significance
(Predictive value)
Babies born to poor family was 64, of them 25(39.1%)
developed sepsis, so, this poor income group was found
significantly (P<0.004) associated with the occurrence
of neonatal sepsis. On the other hand 80 mothers had
irregular antenatal checkup, 36(45%) of their babies
later developed statistically significant (P<0.046) sepsis.
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Journal of Bangladesh College of Physicians and Surgeons
Mothers of 37 infants among cases had prolonged labor
of e 24 hrs as 24 infants among controls. Thus 60.7%
of exposed babies ultimately suffered from sepsis with
3.083 times greater risks than those born after normal
duration of labor. This had highly significant (P<0.008)
association with the sepsis. PROM >24 hrs was found
among 51 mothers, of which 30(58.8%) infants born to
them developed sepsis later on. Though PROM carried
2.071 times higher risk of developing sepsis, it was not
found statistically significant (P <0.072). History of
unclean vaginal examination (UVE) e3 times was found
in 49 mothers. Their 30(61.2%) newborn later had sepsis
with 2.447 times greater risk than those born to mothers
having <3 UVE. The association of sepsis with UVE
was significant (P<0.028).
The number of mothers who had intrapartum fever of
>100.70F was 28. Babies born to them later developed
sepsis, the number of which was 22(78.6%) and showed
5.762 times greater risks of sepsis than those born to
mother without intrapartum fever. It was found highly
significant(P<0.000). Twenty-four babies born to
mother had the history of foul liquor. Out of them
19(79.2%) developed sepsis. It carried 5.516 times
greater chance of developing sepsis than babies born to
mothers without foul liquor.
Multiple regressions for sepsis were done at the end.
There was an overall significant relation of the risk factor
for sepsis (F=46.608, P=0.000). The following factors
were independently related to sepsis:
Irregular antenatal checkup of mother.
Gestational age <37weeks (Yes).
Resuscitation at birth (Yes).
Maternal intrapartum fever (Yes).
Discussion:
Neonatal septicemia is still a serious condition with high
mortality. 2,10 Different risk factors are known to have
profound influence on the development of neonatal
sepsis. Our study also reflected the same cumulative
influence of those risk factors, commonly known as
neonatal risk factors and maternal risk factors, in the
development of neonatal sepsis. Though, all the risk
factors did not show the equal and similar influences as
in other previous studies.
Among the neonatal risk factors (T-1 & T-3),
Prematurity, APGAR score<7 at 5 min and neonatal
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Vol. 29, No. 4, October 2011
resuscitations were significantly found to be associated
with neonatal sepsis. But other neonatal risk factors,
though found insignificant, are also discussed for
comparison with other studies. Sex incidence of neonatal
sepsis shows a male preponderance.11,12,13
Though our study shows higher frequency rate of sepsis
in male(39:11), but it failed to show statistical
significance(P<0.081), which is also a similar findings
with Raghavan,14 St. Geme 15 and Buetow et al. 16
Though some studies show nearly equal rate of
infection.17 Birth weight is a well recognized risk factor
for sepsis.18,19, 20, 21,22 As gestational age is not always
assessed accurately, and birth weight is taken as a better
variable. Though association of low birth weight(LBW)
with neonatal sepsis was significantly found in other
studies,13,14,17,21 , unfortunately our study showed
insignificant result(P<0.841). Many of the LBW
neonates included in the study was near to normal birth
weight, as well as smaller sample size, might influence
our result. Prematurity is a widely accepted risk factor
for neonatal sepsis. 22 In our study prematurity
(gestational age < 37 weeks) had a significant
association (P<0.016) with the development of sepsis,
as in other observation 14,17,21,23,24,25 that justified the
inverse relationship of sepsis and gestational age. 18, 19
APGAR score 0-6 24or <6 26 in 1 min. or at 5 min 15,18
is found to be predisposed to neonatal sepsis. In the
present study APGAR score <7 at 5 min had significant
(P<0.046) influence in the development of sepsis than
score <5 at 1 min (P<0.074), like other similar and
significant previous observations 14,17,18 Asphyxia
causes an immunological insult 27and resuscitation
procedures following birth asphyxia tend to explore
them to pathogenic microbes. 14,24 Resuscitation
procedures at birth pose greater risk of neonatal sepsis.
Many life- supporting procedures such as suctioning
and endo-tracheal intubations can lead to transient and
persistent bacteremia. 24 Vascular channels 19,28
umbilical catheterization and mechanical ventilatory
support, contaminated suction catheters, mouth to mouth
breathing predisposed the infants to higher risks of
sepsis.14,18,20,24,29,30 In our study effects of resuscitation
was found statistically significant (P<0.032) in the
development of sepsis, which is compliant with many
previous studies.14,16Among the maternal risk factors
Predictive Values of Risk Factors in Neonatal Sepsis
(T-2 and T-4) our study shows that the attack rates of
sepsis increased significantly with neonates born to
mothers <20yrs of age (P<0.003), in Primi (P<0.029),
in poor income group family (P<0.004) and those
mothers took irregular antenatal checkup (P<0.046). But
no previous study could be found to support these
factors. Prolonged labor e 24 hrs is a recognized risk
factor for neonatal sepsis. 14,24 We also observed
significant (P<0.008) association between this factor
and sepsis. Our result compiles with previous
researchers. Soman et al 31 and Raghavan et al 14 found
significantly higher incidence of neonatal sepsis
following prolonged labor but Bhakoo et al 24 and Sing
et al 32 described it as a dependent factor, that it needs
other factors in association to cause sepsis. Prolonged
labor predisposes mothers to frequent handling and also
causes fetal compromise and asphyxia. Early rupture
invites ascending infection &infected amniotic fluid
frequently leads to neonatal sepsis. Prolonged rupture
of membrane (PROM) e 24 hrs has received the
maximum attention of investigators, and is an important
risk factor,particularly in early onset neonatal sepsis
(EONS).14, 17,25,33,34 It increases the attack rate by more
than 10 folds. We found PROM in 58.8% cases though
it did not reflect statistical significance (P<0.072).
Unclean vaginal examination (UVE) is a potential
source of bacterial contamination.35 Multiple UVE (>3)
increases the risk of neonatal sepsis.34, 36
Our findings (UVE >3) was consistent with other studies
24,37 & it was found to be highly significant
(P<0.028).Attack rate of neonatal sepsis increases with
rise of maternal intrapartum temperature; a 10 fold is
documented when peak temperature rises to 380 C or
more. Our study also found highly significant (P<0.000)
relation of this factor with sepsis. This is consistent with
observation of other workers. Knudsen et al 37 found
20% incidence of sepsis & Bhakoo et al found 12.5%
incidence in term and 55.5% in pre term babies born to
febrile mothers. It has an independent association with
neonatal sepsis. 24
Intrapartum fever is indicative of maternal infections
that are frequently transmitted to the baby in utero or
during passage through birth canal. 24 Presence of foul
smelling liquor has been considered to be indicative of
amnionitis by various investigators, 14,38,39 and found
to be associated with 10% incidence of sepsis.40 Our
MS Hasan & CB Mahmood
observation was highly significant(P<02.001) and
comparable to findings of other researchers. Singh et al
32 described it to be an independent factor. Actually foul
smelling liquor is a reliable feature of chorioamnionitis,
emitting the smell due to breakdown products of
bacterial metabolism, and the infection is easily
transmitted to the fetus in utero.35
The aim of study was not only to detect sepsis, but also
to find out the predictive values of those factors. We
have analyzed those factors individually and also found
the relative influence of them on neonatal sepsis.
Individual analysis of risk factors showed that many
factors like prematurity, APGAR score<7 at 5 min and
neonatal resuscitations among the neonatal factors ( T-
1& 3) and all the maternal risk factors (T-2 &4) were
significantly found to be associated and influenced the
development of sepsis. But when relative influence of
those factors was searched by multiple regressions
(Table VI & Chart 1.1 & 1.2) to see the predictive values
of risk factors, it was found that irregular antenatal
checkup of mother (P<0.017) ,prematurity (P<0.027,
T-6),resuscitative procedure(P<0.071) & maternalthe
risk factors associated with neonatal intrapartum fever
(P<0.089); the association of which was near statistical
significance. In order to treat all infants with sepsis
rapidly and to minimize therapy for those without
infection, risk factor analysis by history is important
41,42 . We may correlating them with clinical and
laboratory data shall help to recommend intervention
strategies designed to reduce incidence and mortality
of neonatal sepsis by prompt recognition and effective
management of high-risk infants at birth.
Conclusion:
From this study it can be concluded that, maternal
intrapartum fever, foul smelling liquor, young mother
(< 20 yrs), poor income group, prolonged labor, UVE
& Primi mother can be designated as maternal risk
factors for neonatal sepsis. Among neonatal factors,
prematurity, resuscitation at birth & low APGAR score
carried the significant risk of developing sepsis. Relative
influence of these risk factors when analyzed over
neonatal sepsis in detecting their predictive values, it
was found that maternal irregular Antenatal check up,
prematurity, resuscitation at birth, and maternal
intrapartum fever are the main risk factors in the
development of neonatal sepsis in our set up.
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Journal of Bangladesh College of Physicians and Surgeons
Appraisal of these perinatal risk factors for neonatal
sepsis could be of great value in identifying the areas
requiring attention to improve perinatal care in order
to prevent neonatal sepsis in our country. However,
small-scale study does not reflect the whole population
and definite conclusion is yet to be drawn. Based on the
result of our study, a cohort study can be undertaken to
obtain additional evidence to refute or support the
existence of association between the risk factors and
neonatal sepsis.
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